Marked familial aggregation of chronic kidney disease suggests that inherited factors play a major role in nephropathy susceptibility. affords from parasitic contamination with genes in African Americans with biopsy-proven forms of focal segmental glomerulosclerosis (FSGS) using admixture mapping.6-8 Odds ratios [OR] for association with FSGS are 17 for human immunodeficiency virus (HIV)-associated collapsing glomerulopathy (herein referred to as HIV-associated nephropathy [HIVAN]) are 29 and for nondescript URB754 forms of end-stage kidney disease (ESKD) that historically were ascribed to high blood pressure (putative hypertension-attributed or arteriolar nephrosclerosis) are 7.3.1 9 Table 1 contains representative ORs for association. A somewhat weaker association was observed in Hispanic Americans of Puerto Rican Dominican and other Caribbean ancestries residing in New York City.2 Rabbit Polyclonal to CREB (phospho-Thr100). These populace groups had approximately 30% African ancestry far higher than typically seen in Mexican Americans and other Hispanic Americans residing outside of the northeastern United States. Table 1 Reported Odds Ratio (Recessive Model) for extended-1-risk haplotype association in African ancestry populations likely reflected strong linkage disequilibrium with because 89% of those with G1 and 76% with G2 have extended-1-risk haplotypes.1 However residual (albeit weaker) association with nephropathy URB754 in European and Asian populations suggests that additional susceptibility alleles exist in this region because the G1 and G2 risk variants are virtually absent in these groups.4 5 10 11 Whether additional risk variants reside in or reflect linkage disequilibrium with the neighboring to gene region remains unknown. CLASSIFYING KIDNEY DISEASE IN POPULATIONS OF AFRICAN ANCESTRY: HYPERTENSION-ATTRIBUTED NEPHROPATHY RESIDES IN THE SPECTRUM OF FSGS High blood pressure is usually reported by nephrologists as the inciting cause of ESKD in URB754 approximately 35% of African Americans initiating renal replacement therapy in the United Says12; however this clinical diagnosis frequently is usually incorrect.13 14 showed impressive genetic association with kidney disease in all 663 AASK participants with available DNA samples (OR 2.57 = 1.39E?8); association was strengthened in the subset whose nephropathy progressed to a serum creatinine concentration greater than 3 mg/dL or ESKD (OR 4.61 = 5.60E?15) or with a baseline urine protein:creatinine ratio greater than 0.6 g/g (OR 6.29 = 2.62E?14).17 Kidney biopsy specimens in a small number of AASK participants showed histologic changes that initially were interpreted as consistent with hypertension focal global glomerulosclerosis (FGGS) and occasionally FSGS with interstitial fibrosis and vascular changes.22 In retrospect these biopsy changes relate to risk variants in East Coast HIV populations with African ancestry relative to the initial West Coast AIDS epidemic that more often impacted European Americans.27 In a similar vein it is fascinating to note the relative lack of URB754 nephropathy risk variants in Africans from Ethiopia (whether they reside in Ethiopia or URB754 emigrated to Israel) along with their associated low frequency of HIVAN.28 URB754 Ethiopians have approximately 50% Middle Eastern and 50% African ancestry; however demarcation is usually observed in allele frequencies between Western and Eastern Africa. Consistent associations between risk variants and kidney disease in those with West African ancestry and lower nephropathy risk in Ethiopians with HIV contamination who lack risk variants show the powerful role of variation in this one gene on nondiabetic kidney disease.29 Fine et al30 evaluated renal pathology in 98 African American patients with HIV infection and nephropathy based on genotypes. The frequency of FSGS was significantly higher among those with two risk variants whereas immune complex-mediated glomerular diseases were more common in those without risk variants. Progression to ESKD was also significantly more common in those with two risk variants versus zero or one. SICKLE CELL DISEASE-ASSOCIATED NEPHROPATHY PROGRESSIVE IGA NEPHROPATHY AND LUPUS NEPHRITIS Variations in (and MYH9) recently was shown to underlie risk for sickle cell disease (hemoglobin.